Control of low flow rates of high pressure fluids is important in many fields including, but not limited to, supercritical fluid extraction, supercritical fluid chromatography, critical point drying, high pressure small parts cleaning, petrochemical processing, and biofuels production. Accordingly, the device in the present invention can be used advantageously in these fields to improve flow control of the high pressure fluids involved.
A very common method of administering biologically-active substances, such as asthma drugs, to the lungs involves the generation of respirable aerosols from pressurized metered dose inhalers (pMDIs). The typical pMDI comprises a small canister containing a suspension of drug particles or solution of dissolved drug in a compressed liquid propellant such as, formerly, CFC-11 and/or CFC-12, or, currently, HFA-134a. A mechanical means is used to fill a metering chamber with the pressurized suspension, and the chamber is allowed to decompress and spray out into an inhalation zone, flash evaporating the propellant and releasing airborne drug particles. Aerosols are generated by both the gas expansion energy and solvent evaporation.
Hand-held pressurized metered-dose inhalers (pMDIs) are commonly used to deliver bronchodilators and anti-inflammatory drugs to the lungs to treat asthma and chronic obstructive pulmonary diseases. Effective and safe aerosol delivery of pharmaceuticals to the lungs is limited by the solvents and propellants that can be used in inhalers. Until recently chlorofluorocarbon (CFC) propellants 11 (trichlorofluoromethane) and 12 (dichlorodifluoromethane) were the most commonly used propellant gases, but their use has been largely phased out in accordance with the Montreal Protocol due to the ozone-depleting properties of CFC propellants. Alternative propellants for pMDIs have become a necessary pursuit of the pharmaceutical industry. The Montreal Protocol is an international treaty that was drafted in 1987 to phase out the commercial production of all ozone-depleting CFCs. The US FDA, EPA, and DOE each have programs to eliminate production and use of all CFCs. The US FDA will not accept new drug applications for any MDI formulations that use CFCs as propellants. The EPA is expecting the pharmaceutical industry to comply with the Montreal Protocol as soon as proven alternative aerosol delivery techniques are developed for most pharmaceuticals.
Valves used to control high pressure fluid flow at low flow rates are problematic. U.S. Pat. No. 6,032,836 teaches that a metering chamber system can be used to deliver aliquots of high pressure fluid propellants such as liquid carbon dioxide to a low pressure inhalation zone, using a chamfered chamber region with a typical volume of 50 μL around a push pin mounted transversely to a high pressure inlet and low pressure outlet, for manual movement of the chamber from filling to discharging positions. Notably, the dose metering is based on the common approach of physically moving a metering chamber from a filling to discharging position, so it shares the drawbacks of this approach with standard, lower-pressure pMDIs charged with CFC or HFA propellants.
Unfortunately, pMDIs based on prior art have several problems and drawbacks. Notably, metered dose inhalers dispense aliquots of drug-containing propellant suspensions by capturing a small, fixed volume in a movable chamber under pressure and then opening this fixed volume chamber to room atmosphere so that the propellant can expand and drive the drug particles to become airborne. Such an approach has the problem that the movable chamber used to capture the aliquot is of fixed volume, so that the delivered drug amount is subject to change as the density of the propellant changes due to temperature changes, number of doses already administered from the canister, or other means. Plus, even under ideal temperature storage conditions, the dose size is fixed, and cannot be adjusted.